A thorough understanding of Multiple Sclerosis (MS) is necessary to offer individuals informed options for treatment and planning. To assist in this quest, the following historical analysis examined how MS has been conceived from the 14th century through the early 20th century. Primary sources were consulted whenever possible, and many of the original archival materials were accessed by the first author (MB) during an on-site visit to the Rare Book Room of the New York Academy of Medicine. There is a striking similarity between how MS symptoms have presented throughout history compared with the 21st century. Sensorimotor and cognitive sequelae have been observed in patients since the 1800s. Cognitive symptoms were acknowledged in the 1800s, but disregarded in the early 1900s and were not given recognition again until the latter part of the 20th century. If conceptualizations of MS are inaccurate, patients will not be served well. In contrast to the shared symptomatology across time, early conceptualizations of etiology and treatment choices differed dramatically from today, a genuine reflection of the times in which they were created.